Page 1

UNT I L EV E RY C A NC ER I S C U RED

SUMMER 2018


FROM THE DIRECTOR 3,400). While these accolades are a reflection of the exceptional clinical care and scientific breakthroughs that lead to practice-changing new therapies, the need to increase our pace of progress is high.

Karen E Knudsen, PhD Enterprise Director, Sidney Kimmel Cancer Center

O

UR MISSION: To improve the lives of cancer patients and their families through compassion, innovation and breakthroughs in research and care. With the opening of our new Asplundh Cancer Pavilion, the Sidney Kimmel Cancer Center (SKCC) is focused even more closely on reducing cancer incidence and mortality in the Greater Philadelphia region. SKCC was recently rated as “Outstanding” by the National Cancer Institute (NCI), and is ranked as a top 20 cancer center nationwide (of more than

According to the NCI’s 2018 “Report to the Nation,” the impact of cancer research on patient outcomes is taking shape. The overall cancer death rates decreased for both men and women, including among all major racial and ethnic groups. SKCC has placed significant effort on reducing cancer disparities across the Philadelphia region, and contributed significantly to national progress. In this report, we highlight recent progress, including identification of previously unappreciated areas of Philadelphia wherein the burden of cancer is unacceptably higher than state or national averages. Moreover, we proudly announce the recruitment of an exceptional new faculty member, Dr. Ana María López, who is a national leader in understanding and eliminating cancer disparities and an expert medical oncologist specializing in women’s cancers. Dr. López takes the helm of SKCC operations in South Jersey to lead the transformation of cancer care in that region. Welcome aboard Dr. López! The NCI also reported that the rates of new cancer incidence has

decreased in men and remained stable in women. This is something to celebrate, but also to understand. Developing novel strategies for prevention is a major area of focus for SKCC, and in communicating information to the public about reducing cancer risk. Proudly, SKCC reports that we are one of only three cancer centers nationwide to rank “Exceptional” by the NCI for our efforts in Community Outreach and Engagement, the highest possible ranking in this category. Finally, the NCI reports that while prostate cancer incidence declined, there has been a rise in development of advanced, metastatic disease. SKCC focuses heavily on advanced prostate cancer, which is the second leading cause of cancer death in men. SKCC is one of only eight NCI-designated cancer centers with a Prostate Cancer Program of Excellence, and this report details some of our major breakthroughs for identifying patients and risk, and developing novel treatments for advanced disease. As Director, I am continually inspired by the increasingly impactful breakthroughs in cancer research and care that I see every day at SKCC, now serving a wide geography of Greater Philadelphians across Jefferson Health’s 14 hospitals. We hold fast to our mission, and will do so, until every cancer is cured. 

STAY CONNECTED TO THE SIDNEY KIMMEL CANCER CENTER BY VISITING OUR WEBSITE AND FOLLOWING US ON SOCIAL MEDIA!

2

www.kimmelcancercenter.org

facebook.com/sidneykimmelcancercenter

@KimmelCancerCtr

@sidneykimmelcancercenter


CONT ENT S FEATURE ARTICLE

12 ASPLUNDH The Sidney Kimmel Cancer Center has a new northern hub of cancer care. This facility will provide our patients outside of Center City Philadelphia with a new option for treatment.

4 BREAKTHROUGHS Breast Cancer

4

Genetics of Cancer Risk

5

Prostate Cancer

6

Lung Cancer

7

Pancreatic Cancer

14

Population Science

15

Cancer Cell Metabolism

16

8

CLINICAL TRIALS

10

NEW DEVELOPMENTS Recent grants, honors, awards, faculty appointments, and program developments

17

NEW LEADERSHIP

18 ENDOWMENTS Generously funded through private philanthropy

21

Kalbach-Newton Professorship

18

Richard H. Hevner Professorship

19

Herbert A. Rosenthal Professorship

20

SURVIVOR STORY

22 PHIL ANTHROPY 3


BREAKTHROUGH

BREAST CANCER

Microbubbles Make Breast Cancer More Susceptible to Radiation

I

njecting breast cancer with oxygen-filled microbubbles makes tumors three times more sensitive to radiation therapy and improves survival in animal models of the disease, according to a study from Sidney Kimmel Cancer Center – Jefferson Health (SKCC) researchers that was published in the International Journal of Radiation Oncology•Biology•Physics. “Finding a way to reverse oxygen deficiency in tumors has been a goal in radiation therapy for over 50 years,” said senior author John Eisenbrey, PhD, SKCC investigator and Associate Professor of Radiology at Thomas Jefferson University. “We’ve demonstrated here that oxygen microbubbles flush tumors with the gas, and make radiation therapy significantly more effective in animal models.” Microbubbles were originally developed to help improve ultrasound imaging. However, being able to “pop” oxygen-filled microbubbles within tumors using beams of ultrasound presented

Example of photoacoustic image combining B-mode ultrasound (in gray scale) with photoacoustic signal (blue to red color overlay). No significant changes in hemoglobin oxygenation were observed following surfactantshelled microbubble with oxygen core (SE61O2) injection and triggering. 4

researchers with an opportunity. Most solid tumors are oxygen-deficient, in part because they quickly outgrow the supply of oxygen-carrying blood vessels that can penetrate the tumor mass. That lack of oxygen also makes tumors more resistant to radiation, which is why trying to flush tumors with oxygen became such a prized goal in the field.

“We think this is a promising approach to test in patients to amplify the effects of radiation therapy” In this study, Eisenbrey and colleagues showed that popping the microbubble with ultrasound immediately prior to radiation treatment could triple sensitivity of the cancer to radiation. It also nearly doubled the survival times in mice from 46 days with placebo, nitrogen-filled microbubbles, to 76 days with oxygen-filled microbubbles. Radiation therapy works by creating oxygen and other free radicals in tumors out of the oxygen present in the tissues. But when those oxygen levels are low, the free radicals produced by radiation therapy are also lower, offering less therapeutic benefit. With this approach, microbubbles are delivered to the general blood flow via intravenous injection, but are popped locally raising the oxygen level only in the tumor. Interestingly, the investigators showed that oxygen increased throughout the cancer mass, even in areas that didn’t have direct access to blood vessels. “The very act of bursting these microbubbles within the tumor tissue seems to change the local physiology of the tumor and make cells generally

John Eisenbrey, PhD Associate Professor, Radiology

more permeable to oxygen and potentially to chemotherapy as well,” said Eisenbrey. “We think this is a promising approach to test in patients to amplify the effects of radiation therapy.” Eisenbrey and his colleagues are currently using a similar approach in a first-in-human clinical trial of microbubbles for improving radiation therapy of liver cancer. Using an FDA-approved microbubble contrast agent, the researchers are bursting microbubbles in patients with liver cancer in combination with their standard treatment with radioembolization therapy. Though not filled with oxygen, the microbubble popping is thought to create enough disruption to the tumor to offer therapeutic benefit over radioembolization alone. 


BRE AKTHROUGH

GENETICS OF CANCER RISK

Panel Provides Guidance on Genetic Evaluation for Prostate Cancer

A

n international, interspecialty panel of experts convened at the SKCC to develop the first set of comprehensive recommendations to guide physicians offering men genetic consultations for prostate cancer risk. The consensus statement, published in the Journal of Clinical Oncology, has helped to make sense of a rapidly evolving field of practice. “There is increasing recognition that some prostate cancers can be inherited. Genetic testing could provide men and their families with information about cancer risk, inform screening and guide better treatment planning and options,” said lead author Veda N. Giri, MD, Director of the Jefferson Clinical Cancer Genetics Service. Research has shown that a subset of prostate cancers are inherited and that at least some of the genes that confer the inherited risk are known and testable. However, clinical practice including referrals, genetic counseling, genetic testing and genetically informed management needs to encompass research advances and increasingly available commercial genetic tests. The goal of the consensus statement was to provide a comprehensive and balanced clinical approach to genetic referrals and testing relevant to clinical cancer genetics specialists, genetic counselors, urologists, oncologists and primary care providers to provide men with an opportunity to make an informed decision regarding genetic testing, screening and personalized treatment. “With a multitude of genetic tests

on the market already, the technology provides more information right now than we can act upon in the clinic,” said senior author Leonard Gomella, MD, Chair of the Department of Urology, Co-leader of the SKCC Prostate Cancer Program, and Clinical Director of the SKCC Network. “We convened a consensus panel to fill the gap in guidelines and develop best practices for when and how to use these genetic panels and how to help patients navigate the information they receive from them.”

“A key factor in making an informed decision is receiving appropriate genetic counseling prior to genetic testing” While genomic testing of prostate cancer is performed to help optimize and personalize treatment, genetic testing reveals information that can affect entire families. “A genetic test can reveal mutations that could impact a son, daughter, sister, brother or other relatives and reveal higher risks of cancer across a family, which is why men need to understand the implications of genetic testing. A key factor in making an informed decision is receiving appropriate genetic counseling prior to genetic testing,” said Giri. “An important evolving area is precision medicine, where tumor sequencing to identify targetable mutations for treatment may also provide a clue to inherited prostate cancer, again raising the question of how best to provide genetic counseling in this setting.” Key panel findings and recommendations include: • Urologists, typically the first to

Veda N. Giri, MD Associate Professor, Medical Oncology Director, Jefferson Clinical Cancer Genetics Service

diagnose a patient, should perform a more thorough family history intake that includes cancers on the mother’s and father’s sides to assess whether a patient should be referred for genetic counseling and testing. • Systems to streamline referrals to genetic counselors are needed to educate men and their families about genetic risks for cancer and help suggest genetic testing for family members who may also be at increased risk. • Areas in critical need of further research include genetic testing in African Americans, greater understanding of the genetic basis for aggressive prostate cancer, and health economic impact of genetic testing for prostate cancer.  5


BREAKTHROUGH

PROSTATE CANCER

New Finding Furthers Understanding of Genetic Basis of Prostate Cancer

T

he retinoblastoma (RB) susceptibility gene was the first gatekeeper gene discovered for cancer. When it was removed or damaged, cancer thrived. Over the years, researchers have discovered methods that have allowed them to experimentally remove the RB gene in order to study it, but just how the gene’s loss made cancers more aggressive was poorly understood. By studying patient samples, researchers at the SKCC found how one type of RB removal, but not another, caused large-scale genetic changes that could make cancer both resistant to treatment and more likely to spread.

sequences of RB loss and illustrate the clinical relevance of RB loss-induced transcriptional rewiring.

“RB loss causes a major reprogramming of gene expression, allowing induction of pathways that promote features that induce characteristics of lethal disease,” said senior author Karen E. Knudsen. The study is the first to identify the molecular con-

The study, which was spearheaded by first author Christopher McNair, PhD, staff scientist in Knudsen’s laboratory, undertook an extensive analysis of tumor samples and cellfree DNA samples from patients with advanced, lethal-stage prostate cancer. Although there are several ways to remove RB from the cellular machinery, the group found that complete loss, rather than inactivation, of the RB gene was associated with changes in gene networks closely linked to aggressive disease. Surprisingly, the cancer-promoting program that RB loss unleashed was distinct from the cell-cycle control genes that RB is best known for controlling.

Molecular alterations caused by the loss of the tumor suppressor RB in aggressive prostate cancer. Plot represents a circularized version of the human genome, while each subsequent inner ring represents novel findings in the study relevant to disease. 6

The study involved a multinational collaboration between SKCC investigators and other U.S.-based laboratories, as well as clinical and basic science researchers in the U.K., Italy, Belgium, Finland and Sweden. The findings were published in the Journal of Clinical Investigation.

“This discovery, and the clinical trials we have underway, suggest that RB status might be used as means to stratify patients into more effective treatment regimens”

The new findings hold great promise for further clinical development and application. The research demonstrates that RB status can be tracked using cell-free DNA samples, an approach referred to as “liquid biopsy,” in prostate cancer patient samples. This method

Karen E. Knudsen, PhD Enterprise Director, Sidney Kimmel Cancer Center Chair and Hilary Koprowski Professor, Cancer Biology Professor, Cancer Biology, Urology, Radiation Oncology, and Medical Oncology

will facilitate the analysis of patient tumors and the selection of the most appropriate therapy based on the individualized features of each patient’s cancer subtype. Multiple clinical trials are now underway that will determine the impact of RB status as a means to guide more precise cancer therapy. “Unlike breast cancer, all prostate cancers are currently treated in an identical fashion. This discovery, and the clinical trials we have underway, suggest that RB status might be used as means to stratify patients into more effective treatment regimens,” said Wm. Kevin Kelly, DO, Leader of the SKCC Prostate Cancer Program. 


BRE AKTHROUGH

LUNG CANCER

Wearable Device May Catch Side Effects of Radiation Therapy Early

A

potential side effect of radiation therapy for lung cancer—pneumonitis, or inflammation of the lungs—may not show up for weeks or months after treatment ends. Symptoms include coughing, chest pain and congestion, shortness of breath, fever, and sometimes require hospitalization. While diagnosis and treatment is primarily dependent on patients reporting symptoms, Sidney Kimmel Cancer Center researchers began a clinical trial to determine feasibility of a wearable device that collects symptom-related data for early detection and treatment.

“Health care is on the brink of remarkable change, and the foundation of this change is rooted in the universe of digital—everything from the Internet of Things to computational computing, big data and more.” Shivank Garg, MD, Department of Radiation Oncology fourth year resident; Maria Werner-Wasik, MD, Professor of Radiation Oncology; and Adam Dicker, MD, PhD, Professor and Chair of Radiation Oncology, teamed up with Health Care Originals, the company that makes the device. Originally designed to monitor breathing in asthma patients, the 3-inch, triangular-shaped patch called ADAMM (Automated Device for Asthma Monitoring and Management) measures biometrics related to breathing—respiration rate and characteristics, wheezing, heart rate and temperature—and activity level such as steps per day. Realizing many of these biometrics could also be used to detect pneumonitis symptoms, the researchers proposed a pilot study in patients.

In addition to data collected from ADAMM, patients will describe any side effects they experience, which can also appear during treatment. Research has shown that side effects a patient considers worth reporting can differ from those a doctor considers worth reporting, pushing clinical research toward considering and weighing patient-reported outcomes (PROs) more heavily than in the past. Garg values PROs as a way to standardize the study. “If we’re going to compare the data we get from the device and we want to look at quality of life, it’s important we’re using PROs as a measure to compare to because they’re better correlated to how patients are actually doing.” The feasibility trial will assess several questions, such as whether patients can wear the device often enough, properly charge and apply it, and if it’s comfortable. The trial will also assess whether ADAMM-collected data could detect radiation pneumonitis early. “We’re also doing an exploratory analysis of different metrics such as heart rate, breathing, coughing and wheezing, to see how they correlate with any hospitalizations or emergency room

ADAMM device

Adam Dicker, MD, PhD Professor and Chair, Radiation Oncology

visits,” said Garg. Phase II of the trial will be randomized and include 100 patients; correlations found in the first phase will be used to alert clinicians if biometrics indicate increased risk for radiation pneumonitis and potentially suggest an intervention. “Ultimately, we hope to evaluate whether this approach could be used to improve patient outcomes and spot an issue before it becomes a serious problem,” said Dicker, who leads the Scholarly Inquiry Program in Digital Health and Data Science at Sidney Kimmel Medical College. “Health care is on the brink of remarkable change, and the foundation of this change is rooted in the universe of digital—everything from the Internet of Things to computational computing, big data and more.”  7


IN VESTIGATOR INITIATED TRIAL MELANOMA

SKCC-led Clinical Trial to Test Immunotherapy in Stage 2 Melanoma

I

nvestigators at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC) are conducting a new clinical trial with the goal of developing an alternative treatment for melanoma that circumvents the high toxicity associated with current standard-of-care therapy. Melanoma is the most deadly form of skin cancer, responsible for approximately 10,000 deaths per year in the United States. This type of cancer arises in the melanocytes, which are pigment-producing cells located in the basal layer of the skin. One of the primary causes of melanoma is ultraviolet light exposure, which induces gene mutations in melanocytes that lead to their rapid proliferation – the resulting tumor thus often resembles a fast-growing mole on the skin surface. Melanoma is associated with excessive tanning, especially in people who are genetically predisposed to be more sensitive to sunlight and to experience frequent sunburns. If detected early, melanoma can be treated effectively through surgery and chemotherapy, although current chemotherapy regimens are associated with high levels of toxicity. Given the aggressive nature of melanoma and the high toxicity of some current chemotherapies, there is great interest in developing more effective treatments that are also well tolerated by melanoma patients. This new phase II clinical trial will test the effect of the antibody treatment nivolumab (Opdivo) in patients

8

undergoing treatment for stage 2b/2c melanoma. These patients have already had their melanoma removed surgically, and have had lymph node biopsies to confirm that the tumor has not metastasized and spread to other parts of the body. Nivolumab inhibits cancer growth by targeting a cell-surface molecule called programmed cell death protein 1 (PD-1), which regulates function of the human immune system. Nivolumab, a PD-1 inhibitor, blocks PD-1 activity and therefore activates the immune system to seek out and destroy cancer cells. Nivolumab has already been approved by the Food and Drug Administration (FDA) for the treatment of stage 3 and 4 melanoma. However, at present the only treatment approved for stage 2 melanoma is interferon, which is highly toxic to patients. If effective, nivolumab will offer a much less toxic alternative to interferon in stage 2 melanoma patients.

“This is currently the only trial open in the U.S. for patients with stage 2 melanoma to receive a PD-1 inhibitor.” This investigator-initiated trial is led by Adam Berger, MD, Chief of the Section of Surgical Oncology, Department of Surgery at Thomas Jefferson University Hospital, and Professor, Sidney Kimmel Medical College at Thomas Jefferson University. Patients will receive nivolumab every four weeks for 12 cycles, and will be assessed for recurrence of melanoma at the 24 month time point. As Berger explains, “Stage 2b and 2c melanoma

Adam Berger, MD Professor, Surgery Vice Chair for Clinical Research Chief, Section of Surgical Oncology Chair, PRC

patients have an approximately 30 percent to 45 percent rate of recurrence, so our goal is to decrease this rate of recurrence by about 50 percent with this treatment. This is currently the only trial open in the U.S. for patients with stage 2 melanoma to receive a PD-1 inhibitor.” Berger’s phase II trial testing nivolumab in melanoma patients is one of several ongoing clinical trials at the Sidney Kimmel Cancer Center that are being conducted in the hope of developing more effective and less toxic treatments for a wide range of cancers. 


INVESTIGATOR INITIATED TRIAL LIVER CANCER

Targeting the Liver to Treat Advanced Uveal Melanoma

A

new clinical trial underway at the Sidney Kimmel Cancer Center seeks to improve treatment outcomes for patients with uveal melanoma. The trial, led by Marlana Orloff, MD, Assistant Professor of Medical Oncology at Thomas Jefferson University, will evaluate the use of immunotherapy to treat metastatic uveal melanoma. To date, the major challenge in management of metastatic uveal melanoma is that advanced stages of the disease are highly resistant to standard chemotherapies that have been used to treat metastatic skin melanoma. A novel approach using a kinase inhibitor to block a cell signaling pathway involved in uveal melanoma was recently tested but demonstrated only a modest increase in progression-free survival and led to no significant overall survival benefit for patients. The approach being pursued by Orloff and colleagues is based on recent advances in the treatment of cutaneous melanoma, most notably the advent of effective immunotherapy interventions. These treatments use antibodies to target immune checkpoint pathways throughout the entire body, thereby ramping up activity of the patient’s own immune system to search for and kill cancer cells. Although this strategy has shown highly promising results for metastatic cutaneous melanoma, it has not yielded a dramatic effect in metastatic uveal melanoma, suggesting that this method will need to be modified to be effective. Accordingly, Orloff and her team are adapting the immunotherapy approach

to more tightly focus its effects on the liver since predominant liver metastases are ultimately responsible for patient deaths. Their trial will test a new therapy called immunoembolization (IEMBO), which involves embolization of the hepatic artery of the liver with a gelatin sponge particle in conjunction with administration of a substance termed granulocyte-macrophage colony stimulating factor (GM-CSF), a technique that blocks the hepatic artery through which liver tumor cells obtain almost all of their nutrients and oxygen. In contrast, normal liver cells obtain most of their nutrients and oxygen through the portal vein, so this hepatic artery embolization effectively starves metastatic uveal melanoma cells with minimal effects on the rest of the liver. In previous studies, it was found that this liver-directed treatment induced a systemic response against melanoma, including the development of inflammatory responses in remote metastases and the prolongation of progression-free survival in patients. It is thought that local stimulation of the immune system may produce a systemic immune response against the tumor cells, which thereby suppresses the growth of liver metastases. This approach resulted in stabilization of multiple liver metastasis in approximately 60 percent of uveal melanoma patients. Orloff and colleagues hypothesize that there might be synergistic benefits to combining this liver-targeted embolization technique with systemically administered immune checkpoint inhibitor therapy. The IEMBO technique with GM-CSF induc-

Marlana Orloff, MD Assistant Professor, Medical Oncology

es inflammation of the liver-localized uveal melanoma metastases, and this liver-targeted anti-cancer response might be amplified by global activation of the immune system triggered by the immune checkpoint therapy. In their new trial, the investigators will evaluate how patients respond to IEMBO together with a combination of immune checkpoint inhibitory antibodies, whether this two-pronged approach leads to longer progression-free survival and an improved overall survival benefit for advanced uveal melanoma patients, and whether the treatment is associated with significant adverse effects. If successful, the clinical trial will open a new avenue for treating uveal melanoma that has spread to the liver and will form the basis for additional trials. ď Ž 9


NEW DEVELOPMENTS AWARDS AND HONORS AILEEN DENG, MD

WM. KEVIN KELLY, DO

ASCO Merit Award

Elected to be the Medical Oncology Lead for the NCI GU Cancers Steering Committee

MATTHEW HUESSER, MBA

BRITTANY SIMONE, DO

Appointed to the Steering Committee of the NCI Public Affairs and Marketing Network

American Association for Cancer Research-Takeda Oncology Scholar-in-Training Award

MARK MANN, MD

CHRISTINE BONACCORSO, RN, BSN, OCN

Appointed to the NRG Surgical Oncology Committee

American Association of College Nursing Jonas Scholar

GRANTS

10

ELDA GRABOCKA, PHD

DAN ERKES, PHD (Mentor: Andrew Aplin)

W.W. Smith Charitable Trust

American Cancer Society

Targeting Stress Adaptive Mechanisms for the Treatment of Pancreatic Cancer

The Impact of Bromodomain and Extraterminal Region Inhibitors on Melanoma

ADAM SNOOK, PHD (Co PI: Jordan Winter, Wei Jiang)

JUN HE, PHD

De Gregorio Family Foundation

NIH K99

GUCY2C CAR-T Cell Therapy in Gastroesophageal Cancer

New mechanisms of acquired resistance to EGFR-TKIs in Non-small-cell lung cancer

GINO CINGOLANI, PHD

CHRISTINE M. EISCHEN, PHD

NIH R01

NCI R01

Regulation of Nuclear Import Through Importin Alpha Isoforms

Novel oncogenic functions or Mdm2 and Mdmx

JEFFREY BENOVIC, PHD

GLENN RADICE, PHD

NIH R01

NIH R01

Structural and dynamic analysis of GRK interaction with G protein-coupled receptors

Mechanotransduction in Heart Development and Regeneration

GYORGY HAJNOCZKY, MD, PHD

JI-BIN LIU, MD

NIH R01

NCI R21

Molecular composition of the mitochondrial calcium uniporter and cardiac pathophysiology

Contrast Enhanced Ultrasound Identification of Sentinel Nodes in Esophageal Cancer

JOUNI UITTO, MD, PHD

MICHAEL BOUCHARD, PHD

NIH R01

NIH R21

Novel Treatments for PXE

Consequences of HBV modulation of metabolic homeostasis in human hepatocytes

MATTHEW DALVA, PHD

DIANE MERRY, PHD

NIH R01

NIH R01

Examining the function of biological sex specific genes: the NLGN4s

The Role of the AR Interactome in SBM


NEW DEVELOPMENTS GRANTS (continued) ANDREW APLIN, PHD (Co PI: Marlana Orloff)

GYORGY HAJNOCZKY, MD, PHD

The Helman Family-MRA Team Science Award

NCI R01

Targeting BAP1-dependent alterations in metastatic uveal melanoma

Relevance of VDAC2 Heterogeneity for Hepatic Tumor Growth and Targeting

DIANE MERRY, PHD NIH R01 The AR N/C interaction in SBMA - Mechanistic role and therapeutic potential

PAPERS OF NOTE Goyal N, Rossi MJ, Mazina OM, Chi Y, Moritz RL, Clurman BE, Mazin AV. RAD54 N-terminal domain is a DNA sensor that couples ATP hydrolysis with branch migration of Holliday junctions. Nature Communications. 2018 Jan 02;9(1):34. McNair C, Xu K, Mandigo AC, Benelli M, Leiby B, Rodrigues D, Lindberg J, Gronberg H, Crespo M, De Laere B, Dirix L, Visakorpi T, Li F, Feng FY, de Bono J, Demichelis F, Rubin MA, Brown M, Knudsen KE. Differential impact of RB status on E2F1 reprogramming in human cancer. Journal of Clinical Investigation. 2018 Jan 2;128(1):341-358 Pliatsika V, Loher P, Magee R, Telonis AG, Londin E, Shigematsu M, Kirino Y, Rigoutsos I. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects. Nucleic Acids Research. 2018 Jan 4;46(D1):D152-D159. Masuda I, Takase R, Matsubara R, Paulines MJ, Gamper H, Limbach PA, Hou YM. Selective terminal methylation of a tRNA wobble base. Nucleic Acids Research. 2018 Jan 18 [Epub ahead of print]. Giri VN, Knudsen KE, Kelly WK, Abida W, Andriole GL, Bangma CH, Bekelman JE, Benson MC, Blanco A, Burnett A, Catalona WJ, Cooney KA, Cooperberg M, Crawford DE, Den RB, Dicker AP, Eggener S, Fleshner N, Freedman ML, Hamdy FC, Hoffman-Censits J, Hurwitz MD, Hyatt C, Isaacs WB, Kane CJ, Kantoff P, Karnes RJ, Karsh LI, Klein EA, Lin DW, Loughlin KR, Lu-Yao G, Malkowicz SB, Mann MJ, Mark JR, McCue PA, Miner MM, Morgan T, Moul JW, Myers RE, Nielsen SM, Obeid E, Pavlovich CP, Peiper SC, Penson DF, Petrylak D, Pettaway CA, Pilarski R, Pinto PA, Poage W, Raj GV, Rebbeck TR, Robson ME, Rosenberg MT, Sandler H, Sartor O, Schaeffer E, Schwartz GF, Shahin MS, Shore ND, Shuch B, Soule HR, Tomlins SA, Trabulsi EJ, Uzzo R, Vander Griend DJ, Walsh PC, Weil CJ, Wender R, Gomella LG. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017. Journal of Clinical Oncology. 2018 Feb 1;36(4):414-424. De Dominici M, Porazzi P, Soliera AR, Mariani SA, Addya S, Fortina P, Peterson LF, Spinelli O, Rambaldi A, Martinelli G, Ferrari A, Iacobucci I, Calabretta B. Targeting CDK6 and BCL2 exploits the “MYB addiction” of Ph+ acute lymphoblastic leukemia. Cancer Research. 2018 Feb 15;78(4):1097-1109.

Telonis AG, Rigoutsos I. Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast cancer. Cancer Research. 2018 Mar 1;78(5):1140-1154. Thangavel C, Boopathi E, Liu Y, McNair C, Haber A, Perepelyuk M, Bhardwaj A, Addya S, Ertel A, Shoyele S, Birbe R, Salvino JM, Dicker AP, Knudsen KE, Den RB. Therapeutic Challenge With a CDK 4/6 Inhibitor Induces an RB-dependent SMAC Mediated Apoptotic Response in Non-Small Cell Lung Cancer. Clinical Cancer Research. 2018 Mar 15;24(6):1402-1414. McCall NS, Dicker AP, Lu B. Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer. Clinical Cancer Research. 2018 Mar 15;24(6):1271-1276. Waldman SA, Camilleri M. Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders. Gut. 2018 Mar 21 [Epub ahead of print]. Csordás G, Weaver D, Hajnoczky G. Endoplasmic Reticular-Mitochondrial Contactology: Structure and Signaling Functions. Trends in Cell Biology. 2018 Mar 24 [Epub ahead of print]. Teh JLF, Cheng PF, Purwin TJ, Nikbakht N, Patel P, Chervoneva I, Ertel A, Fortina PM, Kleiber I, HooKim K, Davies MA, Kwong LN, Levesque MP, Dummer R, Aplin AE. In vivo E2F reporting reveals efficacious schedules of MEK1/2-CDK4/6 targeting and mTOR-S6 resistance mechanisms. Cancer Discovery. 2018 May;8(5):568-581. Hruska M, Henderson N, Le Marchand SJ, Jafri H, Dalva MB. Synaptic nanomodules underlie the organization and plasticity of spine synapses. Nature Neuroscience. 2018 May;21(5):671-682. de Leeuw R, McNair C, Schiewer MJ, Neupane NP, Brand LJ, Augello MA, Li Z, Cheng LC, Yoshida A, Courtney SM, Hazard S, Hardiman G, Hussain M, Diehl JA, Drake JM, Kelly WK, Knudsen KE. MAPK reliance via acquired CDK4/6 inhibitor resistance in cancer. Clinical Cancer Research. 2018 May 8 [Epub ahead of print]. Mao YT, Zhu JX, Hanamura K, Iurilli G, Datta SR, Dalva MB. Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase. Neuron. 2018 May 16;98(4):767782.e8. 11


FEATURE ARTICLE

NORTHEAST PHILADELPHIA CANCER CARE

Asplundh Cancer Pavilion Brings Compr

A

cancer diagnosis is a life altering experience. But you got this. Because a new, state-of-the-art healing center with a team of experts offering a personalized treatment plan backed by serious science and everything you need to fight cancer all in one location has just opened–right in your neighborhood.

sophisticated clinical trials and support to the existing cancer program at Abington – Jefferson Heath.

“At Abington, we have a long history of excellent cancer care and outstanding medical specialists in oncology and oncologic surgery, a community-based full service hospital, and a robust network of primary care physicians,” said Steven J. Cohen, MD, Chief of Medical Oncology at SKCC Abington – Jefferson Health and Vice Chair of Medical Oncology at Thomas Jefferson University. “As the northern hub of the Sidney KimKaren E. Knudsen, PhD Steven J. Cohen, MD mel Cancer Center Enterprise Director, Sidney Medical Director, Kimmel Cancer Center Asplundh Cancer Pavilion – Jefferson Health, Chair and Hilary Koprowski Chief, Medical Oncology the Asplundh Professor, Cancer Biology and Hematology Division Cancer Pavilion Professor, Cancer Biology, Vice Chair, Medical Oncology Urology, Radiation Oncology, will provide exProfessor, Medical Oncology and Medical Oncology traordinary clinical care, technology and research care you’d expect from a strong commuThe Sidney Kimmel Cancer Cennity cancer program close to home.” ter and Abington – Jefferson Health proudly unveiled the new Asplundh The Asplundh Cancer Pavilion can Cancer Pavilion, an 86,000 square provide nearly all cancer care under foot outpatient center offering a one roof, whether a patient is seeking comprehensive continuum of cancer services for diagnosis, treatment or care located in Willow Grove, Pa. survivor support. That includes surgical The Asplundh Cancer Pavilion brings to the region the resources of the Sidney Kimmel Cancer Center, which has been recognized as a top 20 hospital in the nation for cancer care by U.S. News & World Report, adding an abundant offering of intricate and 12

consultations, chemotherapy infusion, radiation therapy, symptom support, a dedicated oncology pharmacy and clinical research, as well as support services such as navigation, genetic counseling, social work, financial counseling, support groups and social

events. If a treatment plan involves the care of multiple cancer specialists and healthcare professionals, care will be coordinated so patients can all be seen on the same day at Asplundh. “With our personalized approach to medicine, we design a treatment program specifically for each patient–not solely for a type of cancer,” Cohen said. There is a high level of integration between the Center City and Abington locations of the Sidney Kimmel Cancer Center. All specialists from both campuses collaborate to provide comprehensive program planning, high-level clinical care and clinical trial availability. In nearly every case, SKCC can bring the oncology specialist to Asplundh rather than asking a patient to travel an inconvenient distance or to multiple locations. “The opening of the Asplundh Cancer Pavilion reflects the Sidney Kimmel Cancer Center vision to provide comprehensive cancer care and access to leading edge therapies to a diverse and growing patient population in Center City Philadelphia and beyond,” said Karen E. Knudsen, PhD, Enterprise Director of the Sidney Kimmel Cancer Center – Jefferson Health, Chair and Hilary Koprowski Professor of Cancer Biology at Thomas Jefferson University. For those with uncommon cancers or cases that require highly specialized surgical procedures, surgeons from the Sidney Kimmel Cancer Center in Center City will be available routinely at the Asplundh Cancer Pavilion to see patients and coordinate care plans with other specialists.


rehensive Cancer Care to the Community Ongoing advances in research and treatment means patients with challenging or incurable cancers are living longer, which also means taking care of any other medical problems. Abington – Jefferson Health primary care physicians and other specialists are partners in the lifelong care of cancer patients and survivors. This close cooperation among a patient’s entire medical team provides the best care possible for all medical needs now and in the future. “When Abington and Jefferson combined in May 2015, many people became familiar with our tagline, ‘Better Together,’” Cohen added. “For the Sidney Kimmel Cancer Center at Abington – Jefferson Health, that tagline is our reality.” SKCC is one of only 70 National Cancer Institute (NCI)-designated cancer centers in the country. An NCI designation recognizes cancer centers’ scientific leadership, resources, depth and breadth of research, and a strong commitment to outreach in underserved communities. Designated cancer centers form the “backbone” of the NCI’s programs

for studying and controlling cancer.

“As the northern hub of the Sidney Kimmel Cancer Center – Jefferson Health, the Asplundh Cancer Pavilion will provide extraordinary clinical care, technology and research care you’d expect from a strong community cancer program close to home.” “Many innovative research studies are currently under way at the Sidney Kimmel Cancer Center, ranging from basic research in the laboratories to clinical trials that offer patients access to novel therapies,” Knudsen said. “It’s our responsibility as an NCI-designated cancer center to develop and translate scientific knowledge from promising laboratory discoveries into new and better ways to prevent, detect, diagnose and treat cancer for our patients, as well as for patients worldwide.” “The Sidney Kimmel Cancer Center – Jefferson Health enrolls nearly 20 percent of their cancer patients in therapeutic treatment trials, which is a very high number. Through our Center for Clinical Research, Abington has also been a leading contributor to clinical research trials,” Cohen said. “We have formally integrated our clinical trials

programs with review committees from both campuses to ensure that clinical trials are available to offer to patients wherever they choose to participate— an opportunity we’ve always considered to be an important part of patient care. Thanks to our integrated program, patients in the Abington region will be able to access all three phases of clinical trials at the Asplundh Cancer Pavilion, including phase I, which provides patients the opportunity to receive first-in-human new therapies.” The Asplundh Cancer Pavilion is truly connected to its community: A fundraising effort through the Reimagine Cancer Care campaign at Abington – Jefferson Health raised more than $50 million contributed through 5,000 generous gifts from the community. The lead gift was graciously provided by the children and grandchildren of Carl and Emilie Asplundh, who honored their parents by naming the building. The Sidney Kimmel Cancer Center and Abington – Jefferson Health have reimagined cancer care by bringing everything a patient might need under one roof until every cancer is cured. Starting with yours. 

Asplundh Cancer Pavilion • 3941 Commerce Ave • Willow Grove, PA 19090 13


BREAKTHROUGH

PANCREATIC CANCER

Optimizing Personalized Therapy for Pancreatic Cancer

N

ew research from investigators at the SKCC provides insight into a cellular mechanism underlying the ability of pancreatic cancer cells to resist a promising, personalized therapy. The study was published online in Cancer Research. The research team studied the role of an RNA-binding protein termed HuR in influencing the sensitivity of cancer cells to treatment with a class of drugs known as PARP inhibitors. PARP inhibitors block activity of the polyADP-ribose polymerase (PARP) enzymes, which orchestrate multiple pathways dedicated to repairing damaged DNA during cell division and other cellular processes. The primary target of these drugs, the PARP1 protein, senses and initiates DNA damage repair, a process that a subgroup of pancreatic cancers with “BRCAness” (a DNA repair defective

This figure shows the accumulation of DNA damage in a PDA cell line MIA PaCa2, assessed by a marker of double stranded breaks (γH2AX, green). HuR and PARG silencing significantly increased veliparib- and olaparib-induced DNA damage, thus helping overcome PARPi resistance. 14

gene signature) are especially reliant on. Hence, PARP inhibitors are often initially effective in stalling the growth of cancers from patients with mutations in the BRCA pathway, but this effect is typically transient, as even patients who initially respond eventually recur with metastatic disease.

“If we can drug this mechanism via targeting PARG and HuR ... we can optimize current, promising therapies for this devastating disease” In the new study, led by Jonathan Brody, PhD, of the Jefferson Pancreas, Biliary, and Related Cancer Center and the Department of Surgery at Thomas Jefferson University, the team demonstrated that genetic silencing via CRISPR techniques of the HuR gene increased the relative sensitivity of pancreatic ductal adenocarcinoma (PDA) cells to PARP inhibitors. Further exploration of these effects uncovered a new target enzyme, polyADP-ribose glycohydrolase (PARG). Brody highlighted the significance of this regulatory mechanism by explaining that “we have discovered a novel aspect of DNA repair, the regulation of a key gene (PARG) that gets acutely turned on when PDA cells are being treated with PARP inhibitor therapies.” Understanding PARG and HuR has important implications for developing new strategies to break a therapeutic resistance mechanism found in the majority of pancreatic cancers. “We believe this is an important event for how cancer cells deflect and resist common and novel therapies in the clinic. If we can drug this mechanism via targeting PARG and HuR, which

Jonathan Brody, PhD Director, Research Division, Surgery Gastrointestinal Program Co-leader Sidney Kimmel Cancer Center

we are attempting to do now, we can optimize current, promising therapies for this devastating disease,” Brody said. Following up on these predictions, the group examined the behavior of human PDA cells in a mouse model for pancreatic cancer. They observed that PARP inhibition combined with targeted silencing of HuR resulted in a stronger reduction in tumor growth than PARP inhibition alone, lending credence to the idea that targeting the HuR-PARG axis might yield clinical benefits in treating pancreatic cancer, as well as other cancers. The researchers are developing therapeutic strategies, both small molecule-based and nanotherapy-based (supported by Genisphere), to target this pathway in pancreatic cancer. 


BRE AKTHROUGH

POPULATION SCIENCE

New Map Identifies Areas of Highest Prostate Cancer Burden

T

o identify prostate cancer earlier, many institutions do community outreach and education sessions on cancer screenings. Because prostate cancer is most common among African American men and can be more aggressive in African Americans and men in low socioeconomic brackets, many institutions base outreach efforts on these factors. However, a Preventive Medicine study shows this may not be the best approach, offering another method for identifying areas with the highest prostate cancer burden. “We know that not every man in a high risk demographic will develop prostate cancer,” said senior author Charnita Zeigler-Johnson, PhD, MPH, Sidney Kimmel Cancer Center (SKCC) researcher. “We’ve seen that often the same programs and organizations are targeted for education

Map of Prostate Cancer Burden in Philadelphia, by African American census tract (yellow), low socioeconomic status (pink), and highest prostate cancer burden using the Zeigler-Johnson score (black points). Credit: Russell McIntire, Jefferson (Philadelphia University + Thomas Jefferson University)

and outreach efforts and realized we’re probably leaving out large areas of the city that potentially have higher risk. I wanted to create a more effective tool to find those areas.” Zeigler-Johnson and SKCC Consortium partners looked at prostate cancer cases in Philadelphia from the Pennsylvania Cancer Registry from 2005 to 2014 and created a prostate cancer composite score using those data to help identify census tracts with the highest prostate cancer burden.

“We are seeing the highest prostate cancer burden cluster in tight geographic areas. ...We think it’s worth studying why these areas of the city are at higher risk for poor prostate cancer outcomes.” The score was based on three factors: standardized incidence ratio, which measures how much more likely a population is to get cancer compared with national rates; mortality ratio, which determines the rate of death from prostate cancer compared with national rates; and how advanced the prostate cancer was at diagnosis. None of these factors alone can be used to categorize disease burden; they were more predictive when combined. Then, using mapping software to geographically identify census tracts with the highest scores, “we were surprised to find clusters of high burden that did not always overlap with the areas with the largest concentrations of African Americans or those with lowest socioeconomic status measures,” said first author Russell McIntire, PhD, MPH, Jefferson Col-

Charnita Zeigler-Johnson, PhD, MPH Assistant Professor, Medical Oncology

lege of Population Health researcher. “We are seeing the highest prostate cancer burden cluster in tight geographic areas,” said Zeigler-Johnson, whose earlier work suggested similar trends. “We think it’s worth studying why these areas of the city are at higher risk for poor prostate cancer outcomes.”  Now that the researchers identified areas of high prostate cancer risk in Philadelphia, they will develop an educational outreach program. “Testing our assumptions in the community will help us determine if this tool can be more effective than outreach targeted using traditional methods,” said Zeigler-Johnson. The approach is also one that could be applied to other cancers in other locations.  15


BREAKTHROUGH

CANCER CELL METABOLISM

Reactive Oxygen Species Stop Mitochondria in Their Tracks

M

itochondria are crucial for powering brain function; neurons constantly traffic these organelles along their lengthy projections to ensure a steady stream of energy in areas far from the cell body. The signals that control these movements have eluded scientists; however, research published in Cell Reports reveal that reactive oxygen species halt these organelles by blocking their attachment to motor proteins. Senior author Gyorgy Hajnoczky, MD, PhD, Sidney Kimmel Cancer Center Gastrointestinal Cancer Program member and leader of the MitoCare Center for Mitochondrial Imaging Research and Diagnostics at Thomas Jefferson University, and colleagues illustrate that moderate and localized increases in reactive oxygen species can benefit neurons and other cells by temporarily detaining mitochondria in areas of need. Their research also sheds light on possible ways to treat immobilized mitochondria in neuronal injury and disease, when reactive oxygen species are exceedingly high. “Reactive oxygen species, like many other things in our life, are beneficial and important in low levels, helping in cell regulation and function. But when those levels rise, they become detrimental and involved in disease processes from cancer to cardiovascular disease,” said Hajnoczky. “Neural damage and neurodegenerative diseases often produce prolonged elevations in reactive oxygen species. In these situations, halting mitochon-

16

dria speeds up cell injury and can contribute to disease progression.”

“Neural damage and neurodegenerative diseases often produce prolonged elevations in reactive oxygen species.” Since high levels of reactive oxygen species are already known to cause harm, researchers were interested in understanding how moderate levels impact normal cell function. “This is very difficult to test,” said Hajnoczky. “It’s easy to expose a tissue to very levels of high reactive oxygen species from outside the cell but harder to study smaller and localized changes inside the cell.” Within the last few years, new technology has allowed researchers to start exploring these questions. Using mitochondria engineered with a fluorescent protein sensitive to reactive oxygen species, Hajnoczky’s team and collaborators from the Buck Institute for Research on Aging monitored mitochondrial movement in neurons and other cells amidst increases in reactive oxygen species. They revealed that mitochondria respond to even low levels of reactive oxygen species and can rapidly regain the ability to move once elevated Hippocampal neuron expressing levels dissipate. mito-roGFP1 loaded When in the presence of tetramethylrhodamine, researchers methyl ester (TMRM) increased at t 3 hr (Ci) after treatment with H2O2 reactive ox-

Gyorgy Hajnoczky, MD, PhD Raphael Rubin Professor of Pathology, Anatomy, and Cell Biology

ygen species within small areas of the cell, they found that they could halt just a few of the organelles, illustrating that cells are capable of parking a small number of mitochondria without stopping them all. Hajnoczky and his team found the protein that reactive oxygen species activate, called p38a, to halt mitochondria. They demonstrated that this protein interferes with the molecular machinery that attaches mitochondria to their motor proteins, although they haven’t quite figured out exactly how p38a engages this machinery. The group is investigating these mechanisms, in addition to examining whether this process may contribute to stroke and neurodegenerative diseases. 


NEW LEADERSHIP

SOUTHERN NEW JERSEY

Dr. Ana María López to Lead Medical Oncology at SKCC Jefferson Health – New Jersey

T

he Sidney Kimmel Cancer Center – Jefferson Health (SKCC) welcomes Ana María López, MD, MPH, as the Vice Chair of Medical Oncology and Chief of Cancer Services at SKCC Jefferson Health – New Jersey. López comes from the Huntsman Cancer Institute in Salt Lake City, where she was Director of Cancer Health Equality, in addition to Associate VP for Health Equity and Inclusion at the University of Utah (UU) Health; Associate Director of Collaboration and Engagement Services at the Utah Center for Clinical and Translational Sciences; and Professor of Medicine at UU School of Medicine. “The opportunity to work together to develop the Sidney Kimmel Cancer Center at Jefferson Health – New Jersey is a great one,” López said. “I look forward to working with the SKCC Center City team, to co-developing the clinical team at Jefferson Health – New Jersey, and to synchronize both to deliver quality care for our patients. Together, we can create a clinical service where patients receive state of the art care delivered with warmth, respect and compassion, and health professionals thrive.”

“I was drawn by the opportunity, the stimulus for innovation, and my kinship to the institution and the community.” She brings with her an expertise in breast and gynecological cancers, integrative medicine, telehealth and cancer

disparities. Currently she is president of the Philadelphia-based American College of Physicians, which is the largest medical specialty organization in the United States. Additionally, her strong commitment to cancer disparities is reflected in her leadership of the American Society of Clinical Oncology committee on cancer disparities. “Hiring Dr. López to lead medical oncology and cancer services at Jefferson Health – New Jersey reflects the Sidney Kimmel Cancer Center vision to provide patients throughout South Jersey with comprehensive cancer care and access to leading edge therapies,” said SKCC Enterprise Director Karen E. Knudsen, PhD. “Additionally, her expertise in women’s cancers is part of our strong recruitment effort to bring nationally renowned physicians to our oncology program for the treatment of breast, ovarian and cervical cancers.” López will be based out of SKCC in Center City until the Jefferson Health – New Jersey site is remodeled. Once she moves into the New Jersey site, she will continue to collaborate with research and physician teams throughout the Sidney Kimmel Cancer Center Network and will still spend some days in Center City. When asked what excited her about SKCC and made her want to trade in the Great Salt Lake and the snow-capped mountains of Utah to be near the birthplace of liberty and the Jersey Shore, López responded, “I was drawn by the opportunity, the

Ana María López, MD, MPH Vice Chair, Medical Oncology Chief of Cancer Services, SKCC Jefferson Health-New Jersey

stimulus for innovation, and my kinship to the institution and the community.” López graduated from Bryn Mawr College and received her medical degree from the Sidney Kimmel Medical College at Jefferson–what was then known as Jefferson Medical College–and has family in the area, so she is excited to be coming back to the Philadelphia region. “I spent some wonderful formative years in this part of the world,” she said. “Now, with my adult children here, I feel very at home. I look forward to walking, enjoying the change of seasons, and engaging the community in the ebb and flow of life.” 

17


ENDOWMENT

CANCER BIOLOGY

Kalbach-Newton Professorship in Cancer Research Andrew E. Aplin, PhD, Associate Director for Basic Research and leader of the Cancer Cell Biology and Signaling Program at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC), was named the first recipient of the Kalbach-Newton Professorship in Cancer Research. The professorship was made possible through generous donations from the estates of Raymond B. Kalbach and Caroline Newton. This honor recognizes numerous contributions Dr. Aplin has made in the field of melanoma research, along with his significant leadership, education and mentoring roles.

“Dr. Aplin excels at the frontier of melanoma research, and I look forward to his future contributions with this professorship” Dr. Aplin is funded by the National Institutes of Health/National Cancer Institute to investigate cutaneous melanoma. Despite recent advances in treating this skin cancer, understanding how melanomas adapt and develop resistance to therapies is critical. Dr.

Aplin’s research aims to identify mechanisms of melanoma growth thus identifying novel therapeutic targets. Since 2002, Dr. Aplin and colleagues have identified downstream targets of mutant BRAF signaling and investigated their contribution to malignant melanoma. Additionally, they analyzed the determinants of therapeutic response and mechanisms of resistance to BRAF/ MEK inhibitors and CDK4/6 inhibitors in subsets of melanoma and developed novel models to quantitatively measure ERK1/2 signaling in melanoma tumors in vivo. These studies are translating to new clinical trials targeting ErbB3 adaptive responses in order to optimize MEK inhibitor treatments in melanoma and next generation BRAF inhibitors. His laboratory recently published data that suggested changing administration schedules of a combination treatment of a MEK inhibitor and CDK4/6 inhibitor can improve outcomes and mitigate drug resistance.

Dr. Aplin’s research recently extended into uveal melanoma. He received a $1 million grant from the Dr. Ralph and Marian Falk Medical Research Trust for a teambased approach to investigate uveal melanoma, and a multi-institute Team Science Award from the Melanoma Research Alliance From left: Elizabeth Dale, Mark Tykocinski, Andrew to provide the Aplin, Karen Knudsen, Stephen Klasko scientific basis

18

Andrew E. Aplin, PhD Professor, Cancer Biology and Opthalmology Thomas Jefferson University Associate Director for Basic Science Cancer Cell Biology & Signaling Program Leader Sidney Kimmel Cancer Center

for new uveal melanoma treatments. Nationally, Dr. Aplin is a member of the Melanoma Research Alliance grant review panel and the Melanoma Research Foundation Scientific Advisory Council. He is an editorial board member of Cancer Research and Molecular Cancer Research and a former associate editor of Pigment Cell & Melanoma Research. “Dr. Aplin excels at the frontier of melanoma research, and I look forward to his further contributions with this professorship,” said SKCC Enterprise Director Karen E. Knudsen, PhD. The investiture took place February 13, 2018. 


ENDOWMENT

COMPUTATIONAL MEDICINE

Richard H. Hevner Professorship in Computational Medicine sidore Rigoutsos, PhD, Director of Jefferson’s Computational Medicine Center and a thought leader in the field of computational genomics, was named the inaugural holder of the Richard H. Hevner Professorship in Computational Medicine.

I

play, unravel their links to disease, and translate this knowledge into novel diagnostics and precision therapies. His work combines experimental and computational techniques to solve problems from genomics, genetics, molecular biology and medicine.

Rigoutsos is a member of the Molecular Biology and Genetics Program at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC) and holds appointments in the Departments of Pathology, Anatomy and Cell Biology; Cancer Biology; and Biochemistry and Molecular Biology at the Sidney Kimmel Medical College at Jefferson (Philadelphia University + Thomas Jefferson University).

Rigoutsos has more than 20 patents on novel analytic techniques and algorithms used to automatically identify molecular structures. Originally trained in physics and later in computational science, Rigoutsos joined IBM’s Research Division and co-founded the Computational Biology Center more than 25 years ago, then began studying the genomic architecture and computational molecular genetics. He came to Jefferson in 2010 as founding director of the Computational Medicine Center.

Within the Computational Medicine Center, Rigoutsos focuses on regulatory non-coding RNAs and “big data” mining. Particular interests are in miRNAs, isomiRs, tRNAs, tRNA fragments and piRNAs. He and his team aim to comprehensively elucidate the repertoire of the molecules in tissues and diseases, understand the regulatory roles they

Thomas Jefferson University established the Richard H. Hevner Professorship in Computational Medicine to recognize Hevner, the transformational emeritus chair of the Jefferson Board of Trustees

Isidore Rigoutsos, PhD Director and Professor, Computational Medicine Center Professor, Computational Medicine, Pathology, Anatomy & Cell Biology, Biochemistry & Molecular Biology, and Cancer Biology

and member of the Sidney Kimmel Cancer Center Advisory Council. The professorship was funded by a lead gift of $300,000 from the Methodist Hospital Foundation, a $50,000 contribution from Stephen K. Klasko, MD, MBA, President and CEO of Thomas Jefferson University and Jefferson Health, and Colleen Wyse, and through generous contributions from Jefferson’s executive team and management. Jefferson held a ceremony and official investiture of Rigoutsos April 6, 2018. 

Rick Hevner and Isidore Rigoutsos with Thomas Jefferson University Leadership

19


ENDOWMENT

CANCER BIOLOGY

Herbert A. Rosenthal, MD ‘56 Professor in Cancer Research

C

hristine M. Eischen, PhD, Professor and Vice Chair in the Department of Cancer Biology at Thomas Jefferson University, was invested as the Herbert A. Rosenthal, MD ’56 Professor in Cancer Research. Eischen is a co-leader of the Molecular Biology and Genetics Program at the Sidney Kimmel Cancer Center (SKCC) – Jefferson Health. She also serves as special advisor for basic science to Stephen K. Klasko, MD, MBA, President and CEO of Thomas Jefferson University and Jefferson Health.

“Dr. Eischen’s work is vital to understanding cancer at its most fundamental levels in order to work toward treatments and cures” Eischen has spent her career studying the molecular mechanisms of tumor initiation, with the goal of identifying vulnerabilities in cancer cells that could lead to new therapeutic targets. She has made seminal discoveries in multiple fields of cancer research. She is also a National Cancer Institute (NCI)-funded investigator. In 2017, she was awarded an American Association

20

for Cancer Research–Bayer Innovation and Discovery Grant, which supports innovation and translation of ideas from basic research into novel drugs. She will use this grant to research a new targeted compound with the goal of ultimately treating cancers with high unmet medical need. “Dr. Eischen’s work is vital to understanding cancer at its most fundamental levels in order to work toward treatments and cures,” said Karen E. Knudsen, PhD, Enterprise Director of the Sidney Kimmel Cancer Center and the Hilary Koprowski Professor and Chair of the Department of Cancer Biology. “I eagerly anticipate the discoveries her lab will make with the support of this professorship.” The newly endowed Rosenthal Professorship was created through the estate of Jefferson alumnus Herbert A. Rosenthal, MD ’56. Rosenthal was a well-loved neighborhood

Christine M. Eischen, PhD Professor, Cancer Biology Special Advisor to the TJU President Thomas Jefferson University Molecular Biology and Genetics Program Co-Leader Sidney Kimmel Cancer Center

physician who was known to his patients as “Doc.” He practiced internal medicine for more than 50 years in his home office in the East Mount Airy section of Philadelphia, and was revered for his kindness, compassion and excellence as a diagnostician. Rosenthal greatly appreciated his Jefferson medical education and felt such a strong connection to the school that he bequeathed it his entire estate. A portion of the bequest is also being used to establish the Herbert A. Rosenthal, MD ’56 Scholarship.

From left: Mark Tykocinski, Elizabeth Dale, Christine Eischen, Stephen Klasko, Karen Knudsen

Eischen’s investiture took place June 12, 2018. 


SURVIVOR STORIES

THE BUDDY PROGRAM

From Patient to Supporter: Helping Others Navigate a Cancer Diagnosis As an Air Force and commercial airline pilot, Pete Lonngren’s top priority had always been safety. So in 2007 when he discovered a swollen lymph node in his neck, he knew he had to follow his instincts and take action for the sake of his health. Lonngren, an Indiana native who has lived in South Jersey for the past 40 years, consulted with his primary care physician, who recommended that he visit Jefferson’s Department of Otolaryngology — Head & Neck Surgery for further evaluation. It turned out that the swollen lymph node was due to cancer at the base of Lonngren’s tongue — a diagnosis he received from William Keane, MD, Chair of the Department of Otolaryngology — Head & Neck Surgery at Thomas Jefferson University Hospital. Keane performed a selective neck dissection surgery on Lonngren, and afterward Lonngren received radiation treatment and finally chemotherapy from Rita Axelrod, MD, Co-director of Jefferson’s Thoracic Oncology Program. “I had a great medical team of

the best doctors, nurses and technicians to guide me through my treatment,” Lonngren said. Luckily, he felt healthy enough to return to work a year after his initial diagnosis. He still sees Keane every six months for regular check-ups and to make sure the cancer has not returned.

“Over the last decade, my medical needs have brought me to several departments at Jefferson, and that has only reinforced my admiration for the people who work there” Unfortunately, this was not his only experience with cancer, and he found himself back at Jefferson in 2016 — this time because of prostate cancer. He underwent a radical prostatectomy, performed by Leonard Gomella, MD, Chair of the Department of Urology. He has also been treated at Jefferson for basal cell carcinoma and squamous cell carcinoma of the skin. During one of his many visits to Jefferson, Lonngren met social worker Kate Rehm, who asked him if he would be interested in becoming a volunteer for the Sidney Kimmel Cancer Center Buddy Program. The Buddy Program pairs current patients with volunteers who have gone through a similar diagnosis and/ or treatment. Buddies provide friendly, compassionate advice as a way to lessen patients’ fears and uncertainties as they navigate the often difficult treatment process.

From left: Jerry Mintzer, Pete Lonngren, Lou Lanza

Now retired, Lonngren

Pete Lonngren (left) shown here with Jerry Mintzer

volunteers as a “Buddy on the Spot,” which means that once a week, he sits with patients and their loved ones in the waiting area of the Bodine Center for Radiation Therapy. He is available to answer questions about his experiences and provide companionship to those who feel anxious. He also participates in “Coffee & Conversation with a Cancer Buddy” — meeting with patients in the Jefferson’s Cancer Support and Welcome Center. “Pete is wonderful and a source of great support to our patients,” Rehm said. Lonngren said that through multiple diagnoses and treatments, his respect for Jefferson has been unwavering. “Over the last decade, my medical needs have brought me to several departments at Jefferson, and that has only reinforced my admiration for the people who work there.”  21


PHIL ANTHROPY

SKCC RESEARCH GIFT

Grateful Survivor Says “Bravo!” to Jefferson by Leaving a Lifetime Legacy

“I

f it was not for my Jefferson doctors, I would not be here today,” said concert pianist and opera singer Jane Karatzas. “Everyone at Jefferson is family. I’m especially grateful for my radiation oncologist Dr. Pramila Rani Anne and medical oncologist Dr. Rebecca Jaslow. They – and everyone at Jefferson – take very good care of me, and I love them.” Jane Karatzas is a concert pianist, an opera singer – and a cancer survivor. Born on Valentine’s Day in 1935, Karatzas was a natural performer, taking the stage of the Academy of Music to play Mozart in the Young Prodigy program at the age of 8, and entering the prestigious Philadelphia Conservatory of Music (now University of the Arts) to study voice at 19. She and her operatic tenor husband, Johann, performed together all over the world

– but she credits Jefferson University Hospitals and doctors for her “encore.” During an exam following a routine mammogram which didn’t show any abnormalities, her doctor felt a small lump; it was concerning enough that she ordered a biopsy. On Feb. 14, 2008 – Karatzas’s 73rd birthday – she got the phone call. “It was cancer.” Karatzas immediately underwent a lumpectomy, followed up with radiation and five years of chemotherapy. During that time, she was impressed by the excellent medical care combined with a compassionate “personal touch” Jefferson doctors, nurses and staff provided. An avid devotee of science and medicine thanks to the influence of her older brother, an MD/PhD, Karatzas loves to read and learn about medical research and cancer in particular. After

reading and learning more about the research that is currently underway within the Sidney Kimmel Cancer Center, she was impressed and inspired. “The research they are doing is just wonderful,” she said. “But you have to be careful with cancer. It’s smarter than we are. Every time we think we understand it, it changes!” And that is why Karatzas recently added the Sidney Kimmel Cancer Center – Jefferson Health as a beneficiary in her will; she is bequeathing $1 million dollars for a research fund in her and her late husband’s name.

“If it was not for my Jefferson doctors, I would not be here today.” “Jeff is very near and dear to me,” she said. “When I’m gone I want their research to continue so we can outsmart cancer.” A longtime resident of Broomall, Pa., Karatzas served as a church organist and music director for many years, but retired when her husband passed away seven years ago. She now shares her home with two rescue cats, including one who followed in her footsteps as a performer – Sheba, her black mackerel tabby, is the star of the Tidy Cats Kitty Litter commercials. Petite and spry, Karatzas says she lives a very active life “thanks to a great attitude, and outstanding medical care.”

From left: Elizabeth Dale, Karen Knudsen and Jane Karatzas celebrating

Karatzas once sang the lead roles in Carmen and Samson and Delilah – now she sings the praises of Jefferson. 

To learn more about the many ways a gift today can have a significant impact on cancer breakthroughs please contact the Office of Institutional Advancement at 215-503-7604. 22


PHIL ANTHROPY

PROSTATE CANCER FUNDRAISER

The Men’s Health Event

O

n April 10, the Sidney Kimmel Cancer Center (SKCC) held its Men’s Health Event, which raised vital funds to enhance patient care and fund ongoing research for the Prostate Cancer Program. The Men’s Event was hosted by SKCC Enterprise Director Karen E. Knudsen, PhD, and Leonard G. Gomella, MD, Bernard W. Godwin, Jr. Professor of Prostate Cancer; Chairman, Department of Urology; Senior Director of Clinical Affairs at SKCC; Clinical Director, Sidney Kimmel Cancer Network.

“This was a very successful event both in terms of money raised for prostate cancer research at SKCC, as well as in raising awarness of this most important men’s health issue” Kent Gushner and Joe Weiss, SKCC Advisory Council members, were honorary co-chairs. The event was held at the Prime Rib in Center City, Philadelphia, and featured an evening of casino games,

which were provided by the new Ocean Resort Casino in Atlantic City, cocktails, dinner and entertainment. “This was a very successful event both in terms of money raised for prostate cancer research at SKCC, as well as in raising awareness of this most important men’s health issue,” Weiss said. “It was also a fun event and everyone who attended had a great time.” About 150 guests attended the sold-out event in support of SKCC, which is the home to one of only eight National Cancer Institute-designated Prostate Cancer Centers of Excellence in the country. The Men’s Event sponsors were Joseph J. and Donna Nicoletti Ferrier; Drs. Neal Flomenberg, Matthew Carabasi and Michael Ramirez; Boyds Philadelphia; Joe Weiss – Alkemy X; the Novak Family; Drs. Leonard and Tricia Gomella; Dr. Karen Knudsen and Mr. Brian Costello; and

From left: Joe Weiss, Karen Knudsen, Kent Gushner

MainLine Investment Partners. We hope to see everyone again next year, so save the date: April 30, 2019! 

Men’s Health Event attendees enjoying the craps and blackjack tables

23


233 South 10th Street Bluemle Building Room 1050 Philadelphia, PA 19107

UPCOMING EVENTS JULY SKCC at the Phillies 24 Cancer Awareness Night

AUGUST

03 SKCC Invitational Golf Tournament SEPTEMBER Grand Rounds Kick-Off 05 Howard Soule

CSO, Prostate Cancer Foundation BLSB 101

Men’s Prostate Screening 26 9am-3pm, Bodine Building 111 South 11th Street

OCTOBER AACR Party with a Purpose 28 Honoree: Karen Knudsen, PhD Jefferson Gala 30 Honorees: Doug Pederson and Edith Mitchell, MD

FOR MORE INFORMATION VISIT KIMMELCANCERCENTER.ORG

Discovery Magazine July 2018  
Discovery Magazine July 2018  
Advertisement